C-type animal lectins are a large family of Ca2+ -dependent carbohydrate-binding proteins that function in cellular adhesion, serum glycoprotein clearance and host defense. We are using high-resolution x-ray crystallography to understand the structural basis of the weak, but specific, recognition of carbohydrate ligands by these proteins, as well as their oligomeric organization that clusters binding sites in a defined geometry for multivalent carbohydrate recognition. We are also studying the pH-dependent conformational change that renders C-type lectins unable to bind calcium and hence carbohydrates at mildly acid pH, a property which is central to the biology of those C-type lectins that serve as endocytic receptors.